
<ArticleTitle>Growth-suppressive effects of <prot>BPOZ</prot> and <prot>EGR2</prot>, two genes involved in the <prot>PTEN</prot> signaling pathway.</ArticleTitle>
<AbstractText>Defects in <prot>PTEN</prot>, a tumor suppressor, have been found in cancers arising in a variety of human tissues. To elucidate the tumor-suppressive function of this gene, we have been analysing expression profiles of cancer cells after introduction of exogenous <prot>PTEN</prot>. Those experiments identified 99 candidate genes that were transcriptionally transactivated. Among them, we report here the further analyses of eight genes, <prot>EGR2</prot>/<prot>Krox-20</prot>, <prot>BPOZ</prot>, <prot>APS</prot>, <prot>HCLS1</prot>/<prot>HS1</prot>, <prot>DUSP1</prot>/<prot>MKP1</prot>, <prot>NDRG1</prot>/<prot>Drg1</prot>/<prot>RTP</prot>, <prot>NFIL3</prot>/<prot>E4BP4</prot>, and a novel gene (<prot>PINK1</prot>, PTEN-induced putative kinase). Expression of six of them (<prot>PINK1</prot>, <prot>EGR2</prot>, <prot>HCLS1</prot>, <prot>DUSP1</prot>, <prot>BPOZ</prot>, and <prot>NFIL3</prot>) was decreased in ovarian tumors compared with corresponding normal tissues. Colony-formation assays using plasmid clones designed to express each gene indicated that <prot>EGR2</prot> and <prot>BPOZ</prot> were able to suppress growth of cancer cells significantly; in particular, cancer-cell lines stably expressing <prot>BPOZ</prot> grew more slowly than control cells containing mock vector. Flow cytometry suggested that over-expression of <prot>BPOZ</prot> inhibited progression of the cell cycle at the G(1)/S transition. Anti-sense oligonucleotides for <prot>BPOZ</prot> or <prot>EGR2</prot> effectively inhibited their expression, and cell growth was accelerated. Therefore both genes appear to be novel candidates as mediators of the <prot>PTEN</prot> growth-suppressive signaling pathway.</AbstractText>
